What is the appropriate empirical treatment and work‑up for an older man with a recurrent pruritic penile ulcer that occurs once or twice a year?

Treatment for Recurrent Pruritic Penile Ulcer in an Older Man

For an older man with recurrent pruritic penile ulcers occurring once or twice yearly, the most likely diagnosis is recurrent genital herpes simplex virus (HSV) infection, and he should be offered daily suppressive antiviral therapy with acyclovir 400 mg orally twice daily or valacyclovir 500 mg orally once daily to reduce recurrence frequency by ≥75%. 1

Initial Diagnostic Work-Up

Before initiating treatment, confirm the diagnosis and exclude other etiologies:

• Serologic testing for syphilis is mandatory in all patients presenting with genital ulcers, as syphilis can present atypically and co-infection occurs in 3-10% of cases 1, 2
• HSV culture or PCR testing from the ulcer base during an active outbreak provides definitive diagnosis, as HSV accounts for approximately 49% of all genital ulcer cases 2, 3
• HIV testing at initial presentation and repeated at 3 months if initially negative, given the established association between genital ulcers and HIV transmission 1, 2
• Consider Behçet's syndrome in the differential, particularly if there is a history of oral ulcers, as recurrent genital ulcers are a hallmark feature requiring different management 1

Critical caveat: Up to 25% of genital ulcers remain without laboratory confirmation despite comprehensive testing, so empiric treatment based on clinical presentation is often necessary 2, 3

Treatment Strategy

For Acute Episodes (Episodic Therapy)

When the patient presents during an active outbreak, initiate treatment within 1 day of lesion onset or during the prodrome for maximal benefit: 1, 4

Recommended regimens for recurrent episodes:

• Acyclovir 400 mg orally three times daily for 5 days, OR 1
• Acyclovir 800 mg orally twice daily for 5 days, OR 1
• Valacyclovir 500 mg orally twice daily for 5 days, OR 1
• Famciclovir 125 mg orally twice daily for 5 days 1

For Prevention of Recurrences (Suppressive Therapy)

Given the recurrent nature (1-2 episodes per year), daily suppressive therapy is strongly indicated as it reduces recurrence frequency by ≥75% in patients with frequent recurrences: 1

Recommended suppressive regimens:

• Acyclovir 400 mg orally twice daily (documented safety for up to 6 years), OR 1, 4
• Valacyclovir 500 mg orally once daily, OR 1
• Valacyclovir 1,000 mg orally once daily, OR 1
• Famciclovir 250 mg orally twice daily 1

Important note: Valacyclovir 500 mg once daily is less effective in patients with ≥10 recurrences per year; use higher doses or twice-daily regimens in such cases 1

Follow-Up and Monitoring

• Reassess after 1 year of continuous suppressive therapy to evaluate the patient's psychological adjustment and recurrence rate, as disease manifestations often ameliorate over time 1
• Clinical improvement should occur within 3 days symptomatically and 7 days objectively; lack of response suggests incorrect diagnosis, co-infection, HIV infection, or antimicrobial resistance 2
• Large ulcers may require >2 weeks for complete healing even with appropriate therapy 2

Alternative Diagnosis: Behçet's Syndrome

If the patient has concurrent oral ulcers, scarring from previous ulcers, or other systemic manifestations, consider Behçet's syndrome: 1

• First-line treatment: Colchicine for prevention of recurrent mucocutaneous lesions, especially when genital ulcers are the dominant lesion 1
• Topical corticosteroids for acute ulcer treatment 1
• More aggressive immunosuppression may be required if chronic ulceration causes scarring that could lead to obliterative or deforming genital scarring 1

Patient Counseling

Inform the patient that: 1

• Genital herpes is a recurrent, incurable viral disease but can be effectively managed with antiviral therapy
• Asymptomatic viral shedding occurs and can transmit infection to partners even without visible lesions
• Condom use should be encouraged during all sexual exposures
• Suppressive therapy reduces but does not eliminate asymptomatic shedding and transmission risk 1
• The frequency of recurrences typically decreases over time in many patients 1

Common Pitfalls to Avoid

• Do not rely solely on clinical appearance for diagnosis, as history and physical examination alone are often inaccurate 2
• Do not overlook co-infection: 3-10% of genital ulcer patients harbor multiple pathogens simultaneously 1, 2
• Do not assume HSV without testing in older patients, as syphilis and other etiologies become more likely with age and may require different treatment 1, 2
• Do not forget to screen for HIV, as genital ulcers are established co-factors for HIV acquisition and transmission 1, 2